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Fgf 对于调控非洲爪蟾侧板中胚层的前后模式形成是必需的。

Fgf is required to regulate anterior-posterior patterning in the Xenopus lateral plate mesoderm.

机构信息

Children's Health Research Institute, 800 Commissioners Road E., London, Ontario, Canada.

出版信息

Mech Dev. 2011 Sep-Dec;128(7-10):327-41. doi: 10.1016/j.mod.2011.06.002. Epub 2011 Jul 8.

Abstract

Given that the lateral plate mesoderm (LPM) gives rise to the cardiovascular system, identifying the cascade of signalling events that subdivides the LPM into distinct regions during development is an important question. Retinoic acid (RA) is known to be necessary for establishing the expression boundaries of important transcription factors that demarcate distinct regions along the anterior posterior axis of the LPM. Here, we demonstrate that fibroblast growth factor (Fgf) signalling is also necessary for regulating the expression domains of the same transcription factors (nkx2.5, foxf1, hand1 and sall3) by restricting the RA responsive LPM domains. When Fgf signalling is inhibited in neurula stage embryos, the more posterior LPM expression domains are lost, while the more anterior domains are extended further posterior. The domain changes are maintained throughout development as Fgf inhibition results in similar domain changes in late stage embryos. We also demonstrate that Fgf signalling is necessary for both the initiation of heart specification, and for maintaining heart specification until overt differentiation occurs. Fgf signalling is also necessary to restrict vascular patterning and create a vascular free domain in the posterior end of the LPM that correlates with the expression of hand1. Finally, we show cross talk between the RA and Fgf signalling pathways in the patterning of the LPM. We suggest that this tissue wide patterning event, active during the neurula stage, is an initial step in regional specification of the LPM, and this process is an essential early event in LPM patterning.

摘要

鉴于侧板中胚层 (LPM) 会产生心血管系统,因此确定在发育过程中将 LPM 细分为不同区域的信号级联是一个重要的问题。已知视黄酸 (RA) 对于建立重要转录因子的表达边界是必要的,这些转录因子沿着 LPM 的前后轴划定了不同的区域。在这里,我们证明成纤维细胞生长因子 (Fgf) 信号对于调节相同转录因子 (nkx2.5、foxf1、hand1 和 sall3) 的表达域也是必要的,因为它限制了 RA 反应性 LPM 域。当在神经胚期胚胎中抑制 Fgf 信号时,更靠后的 LPM 表达域会丢失,而更靠前的域会进一步向后延伸。由于 Fgf 抑制导致晚期胚胎出现类似的域变化,因此这些域变化在整个发育过程中得以维持。我们还证明 Fgf 信号对于心脏特化的启动以及在明显分化发生之前维持心脏特化都是必要的。Fgf 信号对于限制血管模式形成和在 LPM 的后端创建与 hand1 表达相关的血管自由域也是必要的。最后,我们展示了 RA 和 Fgf 信号通路在 LPM 模式形成中的相互作用。我们认为,这种在神经胚期活跃的组织广泛模式形成事件是 LPM 区域特化的初始步骤,并且这个过程是 LPM 模式形成的一个重要早期事件。

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